REG3G_MOUSE
ID REG3G_MOUSE Reviewed; 174 AA.
AC O09049;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Regenerating islet-derived protein 3-gamma;
DE Short=REG-3-gamma;
DE AltName: Full=Pancreatitis-associated protein 3;
DE AltName: Full=Regenerating islet-derived protein III-gamma;
DE Short=Reg III-gamma;
DE Contains:
DE RecName: Full=Regenerating islet-derived protein 3-gamma 16.5 kDa form;
DE Contains:
DE RecName: Full=Regenerating islet-derived protein 3-gamma 15 kDa form;
DE Flags: Precursor;
GN Name=Reg3g; Synonyms=Pap3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Liver, and Pancreas;
RX PubMed=9055810; DOI=10.1016/s0378-1119(96)00589-6;
RA Narushima Y., Unno M., Nakagawara K., Mori M., Miyashita H., Suzuki Y.,
RA Noguchi N., Takasawa S., Kumagai T., Yonekura H., Okamoto H.;
RT "Structure, chromosomal localization and expression of mouse genes encoding
RT type III Reg, RegIII alpha, RegIII beta, RegIII gamma.";
RL Gene 185:159-168(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, AND PROTEOLYTIC PROCESSING.
RX PubMed=19095652; DOI=10.1074/jbc.m808077200;
RA Mukherjee S., Partch C.L., Lehotzky R.E., Whitham C.V., Chu H.,
RA Bevins C.L., Gardner K.H., Hooper L.V.;
RT "Regulation of C-type lectin antimicrobial activity by a flexible N-
RT terminal prosegment.";
RL J. Biol. Chem. 284:4881-4888(2009).
RN [4]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16504538; DOI=10.1016/j.pep.2006.01.014;
RA Cash H.L., Whitham C.V., Hooper L.V.;
RT "Refolding, purification, and characterization of human and murine RegIII
RT proteins expressed in Escherichia coli.";
RL Protein Expr. Purif. 48:151-159(2006).
RN [5]
RP FUNCTION, MANNAN- AND PEPTIDOGLYCAN-BINDING, TISSUE SPECIFICITY, INDUCTION,
RP AND DEVELOPMENTAL STAGE.
RX PubMed=16931762; DOI=10.1126/science.1127119;
RA Cash H.L., Whitham C.V., Behrendt C.L., Hooper L.V.;
RT "Symbiotic bacteria direct expression of an intestinal bactericidal
RT lectin.";
RL Science 313:1126-1130(2006).
RN [6]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=17635956; DOI=10.1084/jem.20070563;
RA Brandl K., Plitas G., Schnabl B., DeMatteo R.P., Pamer E.G.;
RT "MyD88-mediated signals induce the bactericidal lectin RegIII gamma and
RT protect mice against intestinal Listeria monocytogenes infection.";
RL J. Exp. Med. 204:1891-1900(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=21998396; DOI=10.1126/science.1209791;
RA Vaishnava S., Yamamoto M., Severson K.M., Ruhn K.A., Yu X., Koren O.,
RA Ley R., Wakeland E.K., Hooper L.V.;
RT "The antibacterial lectin RegIIIgamma promotes the spatial segregation of
RT microbiota and host in the intestine.";
RL Science 334:255-258(2011).
RN [9]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=22727489; DOI=10.1016/j.immuni.2012.04.010;
RA Lai Y., Li D., Li C., Muehleisen B., Radek K.A., Park H.J., Jiang Z.,
RA Li Z., Lei H., Quan Y., Zhang T., Wu Y., Kotol P., Morizane S., Hata T.R.,
RA Iwatsuki K., Tang C., Gallo R.L.;
RT "The antimicrobial protein REG3A regulates keratinocyte proliferation and
RT differentiation after skin injury.";
RL Immunity 37:74-84(2012).
RN [10]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=23401489; DOI=10.1084/jem.20120260;
RA Choi S.M., McAleer J.P., Zheng M., Pociask D.A., Kaplan M.H., Qin S.,
RA Reinhart T.A., Kolls J.K.;
RT "Innate Stat3-mediated induction of the antimicrobial protein Reg3gamma is
RT required for host defense against MRSA pneumonia.";
RL J. Exp. Med. 210:551-561(2013).
CC -!- FUNCTION: Bactericidal C-type lectin which acts exclusively against
CC Gram-positive bacteria and mediates bacterial killing by binding to
CC surface-exposed carbohydrate moieties of peptidoglycan. Restricts
CC bacterial colonization of the intestinal epithelial surface and
CC consequently limits activation of adaptive immune responses by the
CC microbiota. The uncleaved form has bacteriostatic activity, whereas the
CC cleaved form has bactericidal activity against L.monocytogenes and
CC methicillin-resistant S.aureus. Regulates keratinocyte proliferation
CC and differentiation after skin injury. {ECO:0000269|PubMed:16504538,
CC ECO:0000269|PubMed:16931762, ECO:0000269|PubMed:17635956,
CC ECO:0000269|PubMed:19095652, ECO:0000269|PubMed:21998396,
CC ECO:0000269|PubMed:22727489, ECO:0000269|PubMed:23401489}.
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the small intestine,
CC including Paneth cells (at protein level). Hardly detectable in the
CC colon (at protein level). Highly expressed in the lung epithelium
CC during methicillin-resistant S.aureus infection (at protein level).
CC Skin injury increases its epidermal expression. Also expressed in the
CC pancreas. {ECO:0000269|PubMed:16504538, ECO:0000269|PubMed:16931762,
CC ECO:0000269|PubMed:17635956, ECO:0000269|PubMed:21998396,
CC ECO:0000269|PubMed:22727489, ECO:0000269|PubMed:23401489,
CC ECO:0000269|PubMed:9055810}.
CC -!- DEVELOPMENTAL STAGE: In mid-small intestine, very low levels at birth.
CC Expression levels rise dramatically during the weaning period (P17-P22)
CC and remain high into adulthood in conventionally raised but not
CC germfree animals. {ECO:0000269|PubMed:16931762}.
CC -!- INDUCTION: Up-regulated in Paneth cells by intestinal microbiota (at
CC protein level). MyD88-mediated signals are essential for its induction
CC in intestinal epithelial cells. Induction in the lung is dependent on
CC IL6ST-induced STAT3 signaling. IL17A induces its expression in primary
CC keratinocytes and skin wounds. {ECO:0000269|PubMed:16931762,
CC ECO:0000269|PubMed:17635956, ECO:0000269|PubMed:22727489,
CC ECO:0000269|PubMed:23401489}.
CC -!- DOMAIN: The EPN motif is essential for recognition of the peptidoglycan
CC carbohydrate backbone and for efficient bacterial killing with Glu-114
CC playing a key role in peptidoglycan binding and bactericidal activity.
CC {ECO:0000250}.
CC -!- PTM: Proteolytic processing by trypsin removes an inhibitory N-terminal
CC propeptide and is essential for peptidoglycan binding and antibacterial
CC activity. {ECO:0000269|PubMed:19095652}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at normal Mendelian ratios.
CC They appear healthy and show no signs of enteropathy, but exhibit a
CC marked increase in the number of mucosa-associated bacteria,
CC predominantly Gram-positive, relative to cohoused wild-type littermates
CC in distal small intestine. {ECO:0000269|PubMed:21998396}.
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DR EMBL; D63361; BAA18930.1; -; mRNA.
DR EMBL; D63362; BAA18931.1; -; Genomic_DNA.
DR EMBL; BC061139; AAH61139.1; -; mRNA.
DR CCDS; CCDS20258.1; -.
DR RefSeq; NP_035390.1; NM_011260.2.
DR AlphaFoldDB; O09049; -.
DR SMR; O09049; -.
DR STRING; 10090.ENSMUSP00000032089; -.
DR MEROPS; I63.002; -.
DR TCDB; 1.C.111.1.1; the regiiiGama (regiiiGama) family.
DR PaxDb; O09049; -.
DR PeptideAtlas; O09049; -.
DR PRIDE; O09049; -.
DR ProteomicsDB; 255178; -.
DR Ensembl; ENSMUST00000032089; ENSMUSP00000032089; ENSMUSG00000030017.
DR GeneID; 19695; -.
DR KEGG; mmu:19695; -.
DR UCSC; uc009ckb.1; mouse.
DR CTD; 130120; -.
DR MGI; MGI:109406; Reg3g.
DR VEuPathDB; HostDB:ENSMUSG00000030017; -.
DR eggNOG; KOG4297; Eukaryota.
DR GeneTree; ENSGT00940000154447; -.
DR HOGENOM; CLU_049894_18_0_1; -.
DR InParanoid; O09049; -.
DR OMA; WEWSNAD; -.
DR OrthoDB; 1509611at2759; -.
DR PhylomeDB; O09049; -.
DR Reactome; R-MMU-6803157; Antimicrobial peptides.
DR BioGRID-ORCS; 19695; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Reg3g; mouse.
DR PRO; PR:O09049; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; O09049; protein.
DR Bgee; ENSMUSG00000030017; Expressed in crypt of Lieberkuhn of small intestine and 60 other tissues.
DR ExpressionAtlas; O09049; baseline and differential.
DR Genevisible; O09049; MM.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB.
DR GO; GO:0070492; F:oligosaccharide binding; IDA:UniProtKB.
DR GO; GO:0042834; F:peptidoglycan binding; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0044278; P:cell wall disruption in another organism; IDA:UniProtKB.
DR GO; GO:0051838; P:cytolysis by host of symbiont cells; IDA:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0045617; P:negative regulation of keratinocyte differentiation; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0010838; P:positive regulation of keratinocyte proliferation; IDA:UniProtKB.
DR GO; GO:0090303; P:positive regulation of wound healing; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central.
DR Gene3D; 3.10.100.10; -; 1.
DR InterPro; IPR001304; C-type_lectin-like.
DR InterPro; IPR016186; C-type_lectin-like/link_sf.
DR InterPro; IPR016187; CTDL_fold.
DR Pfam; PF00059; Lectin_C; 1.
DR SMART; SM00034; CLECT; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1.
PE 1: Evidence at protein level;
KW Acute phase; Antimicrobial; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Inflammatory response; Lectin; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:19095652"
FT CHAIN 27..174
FT /note="Regenerating islet-derived protein 3-gamma 16.5 kDa
FT form"
FT /id="PRO_0000017435"
FT PROPEP 27..37
FT /evidence="ECO:0000269|PubMed:19095652"
FT /id="PRO_0000422753"
FT CHAIN 38..174
FT /note="Regenerating islet-derived protein 3-gamma 15 kDa
FT form"
FT /id="PRO_0000422754"
FT DOMAIN 47..171
FT /note="C-type lectin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT MOTIF 114..116
FT /note="EPN"
FT /evidence="ECO:0000250"
FT DISULFID 40..51
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 68..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
FT DISULFID 145..162
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040"
SQ SEQUENCE 174 AA; 19307 MW; 5575E9E56A4D8CEF CRC64;
MLPRITITIM SWMLLSCLML LSQVQGEVAK KDAPSSRSSC PKGSRAYGSY CYALFSVSKN
WYDADMACQK RPSGHLVSVL SGAEASFLSS MIKSSGNSGQ YVWIGLHDPT LGYEPNRGGW
EWSNADVMNY INWETNPSSS SGNHCGTLSR ASGFLKWREN YCNLELPYVC KFKA
